Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in infants, young children and the elderly, particularly those that are institutionalized. It is the most common cause of viral bronchiolitis and pneumonia in children, and outbreaks frequently reach epidemic proportions during the winter months, accounting for roughly 90,000 hospitalizations and 4,500 deaths per year. Gemini Technologies, Inc. is developing novel antisense chimeras for use in the treatment of RSV infections. These chimeras are comprised of an antisense component to the targeted viral RNA genome, while the 2-5A portion of the chimera attracts and activates RNase L, an endoribonuclease that can cleave the associated genomic RNA strand. In the phase I studies, we succeeded in synthesizing and testing a second generation anti-RSV chimera that had potent antiviral activity in cultured cells and in primates. Here we propose to carry this compound through more definitive animal studies, utilizing aerosol delivery to mimic the clinical application of this compound. In addition, we propose medicinal chemistry-based studies aimed at improving chimera synthesis, and preliminary toxicology studies.
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| Cramer, Hagen; Okicki, James R; Kuang, Mei et al. (2005) Targeted therapy of respiratory syncytial virus by 2-5A antisense. Nucleosides Nucleotides Nucleic Acids 24:497-501 |
| Xu, Zan; Kuang, Mei; Okicki, James R et al. (2004) Potent inhibition of respiratory syncytial virus by combination treatment with 2-5A antisense and ribavirin. Antiviral Res 61:195-206 |
